POS1058 CORRELATION BETWEEN SERUM KL-6 AND ANTI-MODIFIED PROTEIN ANTIBODIES (AMPAS) IN RHEUMATOID ARTHRITIS-ASSOCIATED INTERSTITIAL LUNG DISEASE
Authors: J. C. Sarmiento-Monroy, A. Pérez-Isidro, R. Castellanos Moreira, V. Ruiz, B. Frade-Sosa, A. Azuaga, J. Ramírez, M. J. Gomara, C. Garcia-Moreno, I. Haro, A. Colmenero, M. Morales-Ruiz, E. Ruiz-Ortiz, O. Viñas, F. Hernández-González, J. Sellarés, J. D. D. Cañete, R. Sanmartí, J. A. Gómez-Puerta
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Some studies have shown that Krebs von den Lungen-6 (KL-6) may be a valuable biomarker for diagnosis and stratifying prognosis in Rheumatoid Arthritis-Associated Interstitial Lung Disease (RA-ILD). Citrullination and carbamylation are responsible for generating Anti-Modified Protein/Peptide Antibodies (AMPAs) and are associated with RA-ILD. <h3>Objectives</h3> To evaluate the correlation between serum KL-6 and AMPAs in patients with RA. <h3>Methods</h3> We conducted a cross-sectional study that included patients with RA (ACR/EULAR 2010 criteria) with available KL-6 and AMPAs data measured in blood serum at study enrolment. ILD was diagnosed by high-resolution computed tomography and confirmed by a multidisciplinary committee. Serum KL-6 levels were measured by Lumipulse G KL-6 Kit (Fujirebio, Japan), using Chemiluminescent enzyme immunoassay (CLEIA). The reference value for KL-6 in healthy subjects was 118-627 U/mL. The inter-assay variation coefficient of the reagent was ≤ 4.4%. AMPAs repertoire tested included ACPA, anti-carbamylated protein antibodies (anti-CarP), and autoantibodies to malondialdehyde–acetaldehyde (anti-MAA). ACPA, anti-CarP, and anti-MAA were determined by homemade ELISA tests. Antigens, cut-off values, and isotypes tested are depicted in Figure 1. Spearman's rank correlation coefficient was used to analyze the correlation between serological markers. <h3>Results</h3> A total of 128 patients were included (24 RA-ILD and 104 RA-non-ILD). Patient characteristics were as follows: female 73%, mean age 60.3 ± 12.4 years, mean disease duration 6.5 ± 4.7 years, RF positive 68%, anti-CCP positive 83.6%, erosive disease 54.7%, and mean DAS28 2.94. Most patients received treatment with methotrexate 84 (65.6%), glucocorticoids 72 (56.3%), and biological DMARDs 23 (18.0%). Among RA-ILD patients, the median FVC and DLco (% predicted value) were 79 (IQR 74.7–88.7) and 62.9 (IQR 53.1–70.6), respectively. Usual interstitial pneumonia (UIP) was found in 11/24 (45.8%) patients. The mean KL-6 level was 476.4 ± 400.9 U/mL. KL-6 levels were elevated in 22 patients (17.2%). Serum levels of KL-6 in the RA-ILD group were significantly higher than those in the RA-non-ILD group (756.0 ± 673.4 U/mL vs. 411.9 ± 273.0 U/mL; p&lt;0.001). Serum KL-6 had a moderate positive correlation with HSA-MAA IgA (<i>r</i>=0.56; p=0.048) in patients with non-UIP pattern (<b>Figure 1</b>). Anti-CarP (Fib IgG: 81.8% vs. 54.7; p=0.019) and anti-MAA antibodies (HSA-MAA IgA: 36.4% vs. 10.4; p=0.018) were significantly associated with elevated KL-6 values (<b>Table 1</b>). <h3>Conclusion</h3> Serum KL-6 is a surrogate biomarker of ILD, elevated in a subgroup of patients with RA-ILD. KL-6 elevation correlated with some AMPAs, such as anti-CarP and anti-MAA. Whether AMPAs are potential biomarkers for RA-ILD requires further analysis. <h3>Funding</h3> Hospital Clinic of Barcelona (Grant # 37 933) and the Spanish Ministry of Economy and Competitiveness (Grant # RTI2018-094120-B-I00). <h3>References</h3> [1] Qin Y, et al. <i>Arthritis Res Ther.</i> 2022 [2] Haro I, et al. <i>Int J Mol Sci.</i> 2022 <h3>Acknowledgements</h3> We want to thank all patients who have participated in the study. <h3>Disclosure of Interests</h3> Juan C. Sarmiento-Monroy: None declared, Albert Pérez-Isidro: None declared, Raul Castellanos Moreira Employee of: Bristol Myers Squibb, Virginia Ruiz: None declared, Beatriz Frade-Sosa: None declared, Ana Azuaga: None declared, Julio Ramírez: None declared, Maria Jose Gomara: None declared, Cristina Garcia-Moreno: None declared, Isabel Haro: None declared, Anna Colmenero: None declared, Manuel Morales-Ruiz: None declared, Estíbaliz Ruiz-Ortiz: None declared, Odette Viñas: None declared, Fernanda Hernández-González: None declared, Jacobo Sellarés: None declared, Juan de Dios Cañete: None declared, Raimón Sanmartí: None declared, José A Gómez-Puerta: None declared.